This is a competing renewal of a multi-method longitudinal study of developmental trajectories of reactivity and regulation using behavioral and biological indices and predictors of social competence among cigarette exposed and non-exposed children. The rates of cigarette smoking continue to be quite high, particularly among younger, lower-income women, and our understanding of developmental pathways to regulatory disturbances reported among cigarette exposed children is limited. The original application focused on reactivity and regulation of infants and toddlers at 2, 9, 16, and 24 months. In order to maintain the sample and obtain maternal reports of children's self-regulation, we initiated a brief assessment at 36 months in Year 4 of the project. In the current renewal, we aim to complete the 36 month assessments, and initiate and complete assessments upon entry into kindergarten. The specific aims of this application are to 1) examine direct effects of cigarette exposure on adrenocortical, autonomic, and behavioral reactivity and regulation, self-regulation, and social competence in the preschool/school age period; 2) to examine if the relationship between cigarette exposure and these child outcomes are mediated by reactivity/regulation in infancy; and 3) to examine if these associations may be moderated by infant perinatal risks, maternal risks (psychopathology, parenting), or cumulative environmental risk. The final sample consists of 251 mother-infant dyads (168 in the smoking group and 83 in the non-smoking group) recruited in the first trimester of pregnancy. Prenatal exposure was ascertained by a combination of self-report (from 3 prenatal interviews), maternal oral fluid (at 3 prenatal interviews), and meconium assays (at delivery). Analyses of infant outcome data indicate significant effects of prenatal exposure on infant autonomic regulation during sleep at 2 months, and during affect arousing tasks at 9 months of infant age. Cigarette exposed infants had lower baseline cortisol, and a profile of high behavioral reactivity and low frequency regulatory behavior at 9 months. Prenatal exposure was associated with lower behavioral competence at 16 and 24 months and environmental exposure was associated with higher behavior problems. Data analyses for the current proposal will build on these infant/toddler outcomes by focusing on developmental trajectories of self-regulation from 24 month to kindergarten, on reactivity and regulation in infancy as mediators of salient outcomes at kindergarten, and reasons for heterogeneity in outcomes among cigarette exposed children. This study addresses several gaps in the literature including examination of multiple levels of self-regulation, long-term developmental pathways associated with cigarette exposure, and consideration of key mediators and moderators of these pathways. Understanding developmental trajectories will inform the timing of prevention/intervention efforts. Understanding mediating processes that predict outcomes, or may act to increase risk or promote resilience will inform the content of interventions.